63 Prevention of rheumatoid arthritis cessation) especially when paired with SE [10,31,32]. Additional environmental risk factors are an unhealthy diet, obesity, lack of exercise, and stress, while moderate alcohol consumption may be a protective factor [33–36]. The stratification of at-risk individuals based on their risk factors may allow the identification of those patients who might benefit the most from early preventive actions and/or pharmaceutical interventions. Indeed, in one prediction model which used demographic, clinical, and serological data, patients were stratified into three categories based on their risk of developing RA. Individuals in the low-risk group had only 12% probability of developing RA in the next 5 years. This probability increased to 81% in the group with high risk, identifying the patients who might benefit the most from early intervention strategies [37]. At the moment, no formal treatment recommendations exist for individuals in the pre-clinical stage of RA after presenting with arthralgia; patients are monitored, but as a rule they do not receive any DMARD treatment until clinical signs and symptoms of arthritis and/or formal diagnosis of RA is established. The current study was designed to better understand the feasibility of interventional studies in at-risk individuals, taking into consideration both patient perspectives and the results of recently performed or currently ongoing intervention trials. We distinguished true preventive trials, in which at-risk individuals, including those with CSA, who did not experience clinical arthritis yet, were subjected to targeted interventions, from very early treatment strategies in which UA or early RA patients received treatment. We took note of the SLR and meta-analysis by Hilliquin et al. from 2018, which addressed the same but felt that the number of original reports published since then warranted a renewed investigation [38]. Methods Search Strategy We performed a systematic literature search on Medline and Embase; we focused on articles published between 2010 and 2021. The keywords we used were the following: “exp Arthritis, Rheumatoid/ or ((rheuma* adj3 (gout or disease* or arthritis)) or RA).ti,ab,kf”; “pretreatment or early or suspect or probable or (preclinical or onset or profylaxis or pre-treatment or arthralgia)).ti,ab”; “(prevent* or remission or progression).ti,ab,kf”. Study selection criteria We selected papers that reported randomized controlled trials (RCTs), trial protocols, summary of trials, and patients’ prospective on the topic. The search was limited to 4
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